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Vitamin B12 with methylcobalamin

10/04/2017 17:10
Posted By EP


Deficient in vitamin B12? Trying to decide on a B12 supplement?

Not all B12 supplements are the same: there is Vitamin B12 with cyanocobalamin, hydroxocobalamin, methylcobalamin and adenosylcobalamin.


What form is the best?

With vitamin B12 playing a vital role in the formation of healthy blood cells, energy production, nervous system, cognitive function and homocysteine regulation, it is important to supplement with the right form and combination for bioavailability and absorption.

Vitamin B12 (cobalamin) is the largest and most complex vitamin out there. It is unique, because it is the only vitamin that contains a metal ion, cobalt (hence its name). The vitamin is a cofactor for two enzymes in mammals like us, one is methionine synthase, the other methylmalonyl-CoA mutase. The molecule that is attached to the cobalamin is called a donor. The two most common donors in supplements are cyanide (making cyanocobalamin B12, or cyano B12), and methyl (making methylcobalamin B12, or methyl B12). Other forms you might find are hydroxocobalamin and adenosylcobalamin.


Types of Vitamin B12

  • Methylcobalamin
  • Cyanocobalamin
  • Hydroxocobalamin
  • Adenosylcobalamin

Another vitamin B12 form found in foods is sulphitocobalamin. It won’t be covered here because it’s irrelevant, and no sulphitocobalamin supplement exists.

All those forms are present to some degree in the foods you eat, but the predominant forms are adenosylcobalamin and hydroxocobalamin. 

Only adenosylcobalamin (AdeCbl) and methylcobalamin (MetCbl) are active within the human body.

You’ll find MetCbl mainly in your blood plasma, cytosol cells, and certain body fluids (like cerebral spinal fluid), and AdeCbl in cellular tissues where it is stored in the mitochondria. 



One of the forms of B12 that is readily available and inexpensive is cyanocobalamin. Cyano B12 is a cheap, synthetic, slightly-toxic, inactive form of B12 that is made with a cyanide donor and is used commercially. It is the most stable form, because the cyanide molecule has the greatest attraction to the cobalamin and protects it from extreme conditions (like high temperatures).

However, it doesn’t absorb well and requires methyl groups to detoxify it. The body must use a methylation reaction to cleave the cyanide out of this form so that it can be converted to a usable, absorbable form. This is a demanding process. The irony is that many people supplement with B12 for the express purpose of supporting methylation.

When cyano B12 does absorb, it converts to hydroxocobalamin (hopefully discarding of the cyanide in the process) and then to methylcobalamin and adenosylcobalamin.

When taken orally, absorption of this form is drastically reduced if you have any gastric acid problems.



(also HYDROXY B12, OH-CBL, OR B12A) Hydroxocobalamin is an inactive, natural form of B12 a predominant form in vitamin B12 rich foods. If your body easily converts hydroxocobalamin to the active forms of B12 then this may be all you need to supplement a B12 deficiency. However, for those who need help in the conversion process or have methylation or neurological dysfunction then methylcobalamin and adenosylcobalamin will likely be required.

Compared to cyano B12, it has a higher affinity to plasma protein and a longer half life, retaining longer in the blood. Again, it doesn’t contain a toxic donor, so no detoxification reaction is required for it to be absorbed.

Hydroxocobalamin reacts chemically with cyanide (CN), nitric oxide (NO) and nitrous oxide (N2O). In fact, this form of B12 is commonly used as an antidote for cyanide toxicity.

Like cyanocobalamin, hydroxy B12 eventually has to be converted in the body to both methylcobalamin and adenosylcobalamin. But it converts much easier.

The European Journal of Clinical Nutrition concluded that the best way to address a B12 deficiency is the combination of the active forms MeCbl and AdCbl.



(ALSO MECOBALAMIN, MECBL, METCBL, METB12, MEB12, OR METHYL B12) Methylcobalamin, the kingpin, one of the two active, natural forms of B12.

It helps reduce homocysteine concentrations and generates SAMe (S-adenosyl methionine), the most important methyl donor in your body, supplying methyl groups for crucial chemical reactions to help maintain your health. Where methyl B12 shows its greatest utility is with people suffering form degenerative neurological symptoms, where it’s often the only promising treatment. It bypasses several potential issues in the absorption cycle and helps relieve or completely reverse symptoms. High doses of methylcobalamin have been used to help with treatment of multiple sclerosis (improved visual and auditory symptoms, not motor ones), amytropic lateral sclerosis, Alzheimer, Parkinson’s, and may help regenerate.

MetCbl is so effective — in numerous areas — that it is used almost exclusively in Japan to treat B12 deficiency.



(ALSO ADECBL, COBAMAMIDE, COBINAMIDE, DIBENCOZIDE, OR ADOB12) Adenosylcobalamin is the mitochondrial form of B12. It is used by the enzyme methylmalonyl-CoA mutase to convert  to succinylcholine CoA (used in the synthesis of porphyrin). This is why methylmalonic acid (MMA) levels get high when you’re low on AdeCbl. Adenosylcobalamin also acts as an intermediate in the degradative pathway for valine, threonine, methionine, thymine, isoleucine, cholesterol and odd-chain fatty acids.

Most of our B12 reserves are actually stored in the liver as adenosylcobalamin, and are converted to methylcobalamin whenever needed.






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